FRAGMENT BASED DRUG DISCOVERY TARGETING HIV PROTEASE

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 IV型菌毛(T4P)是许多细菌病原体的关键毒力因子，参与多种功能，包括表面运动、微集落形成、黏附、噬菌体黏附和自然转化。IV型菌毛具有重要的科学价值，因为这些细丝在细菌发病机制中发挥着核心作用，而且它们有可能成为抗菌干预的靶标。此外，从生物物理的角度来看，菌毛组装装置代表了一种非凡而独特的分子马达。我们正在努力解决IV型毛孔组装设备内膜平台组件的晶体结构。这些数据将与固体核磁共振、电子显微镜、突变分析和生物化学获得的结构数据相结合，以获得对这一关键分子机器的详细了解。这项工作可能有助于设计新的抗菌疗法，并有助于我们了解另一种关键的细菌毒力系统--2型分泌物，它与IV型菌毛系统高度相似。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Type IV pili (T4P) are key virulence factors for many bacterial pathogens, mediating a broad range of functions including surface motility, microcolony formation, adhesion, phage attachment and natural transformation. Type IV pili are of great scientific interest due to the central role these filaments play in bacterial pathogenesis and for their potential as targets for antibacterial interventions. Furthermore, from a biophysical standpoint, the pilus assembly apparatus represents a remarkable and unique molecular motor. We are working to solve the crystal structures of the components of the inner membrane platform of the Type IV pilus assembly apparatus. These data will be combined with structural data obtained from solid state NMR, electron microscopy, mutational analysis and biochemistry to obtain a detailed understanding of this critical molecular machine. This work will likely contribute to the design of new antibacterial therapies and to our understanding of another critical bacterial virulence system, the Type 2 secretion, which is highly similar to Type IV pilus system.